Non-invasive neuromodulation via targeted delivery of neurotransmitter chemicals

通过神经递质化学物质的靶向递送进行非侵入性神经调节

• 批准号: 9902417
• 负责人: Nicholas E. Todd
• 金额: $ 16.44万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9902417
• 关键词: Affect; Antibodies; Applications Grants; Area; Bayesian Modeling; Behavior; Blood - brain barrier anatomy; Brain; Brain Neoplasms; Brain imaging; Brain region; Chemicals; Clinical; Clinical Treatment; Clinical Trials; Computing Methodologies; Data; Decision Making; Disease; Drug Delivery Systems; Epilepsy; Focused Ultrasound; Foundations; Functional Magnetic Resonance Imaging; Future; Glutamates; Goals; Health; Human; Image; Imaging Techniques; Knowledge; Lead; Liposomes; Magnetic Resonance Imaging; Measures; Mechanics; Mediating; Mentored Research Scientist Development Award; Mentors; Mentorship; Methodology; Methods; Microbubbles; Modeling; Modernization; Molecular; Neurobiology; Neurons; Neurosciences; Neurosciences Research; Neurotransmitters; Nodal; Pain; Parkinson Disease; Pathway interactions; Penetrance; Peripheral; Pharmaceutical Preparations; Process; Rattus; Research; Rest; Rodent; Scientist; Sensory; Site; Somatosensory Cortex; Specificity; Stimulus; System; Tactile; Techniques; Technology; Testing; Thalamic structure; Therapeutic; Training; Training Programs; Translating; United States National Institutes of Health; Work; base; behavior test; behavioral response; career; causal model; chemotherapeutic agent; chronic pain; experience; gamma-Aminobutyric Acid; information processing; macromolecule; millimeter; nerve stem cell; nervous system disorder; neuroimaging; neuroregulation; novel strategies; pain model; painful neuropathy; plasmid DNA; response; sensory cortex; side effect; skills; somatosensory; synaptic function; targeted delivery; tool

Project Summary: Dr. Nicholas Todd is applying for an NIH Mentored Research Scientist Development Award to achieve three interrelated goals: 1) undergo training to gain expertise in two key areas of neuroscience; 2) develop a novel approach to non-invasive neuromodulation based on targeted delivery of neurotransmitter chemicals to the brain; 3) build a strong foundation from which to launch a career as an independent research scientist. The grant proposal has been tailored to achieve these goals by aligning the mentorship expertise, training program, and research aims. Dr. Todd is a magnetic resonance imaging (MRI) physicist by training with particular experience in MR- guided focused ultrasound (FUS) applications and MR neuroimaging. His ambition is to have a long research career as an independent scientist using the tools of FUS and MRI to further our understanding of brain function and advance treatments for neurological diseases. In order to round out his skill set for such a career, he is now seeking training in two key areas of systems level neuroscience, the neurobiology of brain networks and modern computational methods for analyzing neuroimaging data, and also expertise in the specific area of FUS-mediated blood-brain barrier (BBB) opening. Under exceptional mentorship, Dr. Todd will gain a comprehensive understanding of the neurobiology of the pain network (primary mentor, Dr. David Borsook), become proficient in applying Dynamic Causal Modeling for analysis of neuroimaging data (mentor Dr. Lino Becerra and collaborator Dr. Karl Friston), and become an expert in FUS-mediated BBB opening (mentor Dr. Nathan McDannold). The research aims in the proposal build on Dr. Todd’s experience with MR neuroimaging and FUS applications, while providing him with direct experiences in the areas of training. The research work will develop and validate methodology for a novel approach to non-invasive neuromodulation that uses FUS- mediated BBB opening to deliver neurotransmitters to targeted brain regions. The targeted neurotransmitter delivery method will be used to investigate modulation of the rodent pain network. Excitatory (glutamate) and inhibitory (GABA) neurotransmitters will be delivered to nodes of the pain network (thalamus and somatosensory cortex) in healthy and neuropathic pain rats. The effects will be measured throughout the entire pain network using the three complimentary approaches of functional MRI (fMRI), Dynamic Causal Modeling (DCM), and behavioral testing. This work will advance Dr. Todd along his path towards becoming an independent scientist. The training component will provide Dr. Todd with the necessary knowledge of systems level neuroscience to pursue a career using MRI and FUS for brain related research; the research component will develop a new method for non-invasive neuromodulation that will form the basis of future work and grant applications.

项目总结： 尼古拉斯·托德博士正在申请美国国立卫生研究院导师研究科学家发展奖，以实现 三个相互关联的目标：1)接受培训，以获得神经科学两个关键领域的专业知识；2)发展 一种基于神经递质靶向传递的非侵入性神经调节新方法 对大脑的化学物质；3)建立一个坚实的基础，从那里开始独立的职业生涯 研究科学家。赠款提案是为实现这些目标而量身定做的，方法是将 指导专业知识、培训计划和研究目标。 托德博士是一名磁共振成像(MRI)物理学家，在磁共振方面具有特殊的经验- 引导聚焦超声(FUS)应用和磁共振神经成像。他的雄心壮志是要有一个长期的 作为一名独立科学家的研究生涯，使用FUS和MRI工具来加深我们的理解 大脑功能和神经疾病的高级治疗。为了完善他的技能套装 这样的职业生涯，他现在正在寻求系统水平神经科学的两个关键领域的培训， 大脑网络的神经生物学和分析神经成像数据的现代计算方法， 以及在FUS介导的血脑屏障(BBB)开放的特定领域的专业知识。在……下面 在卓越的指导下，托德博士将全面了解 疼痛网络(主要导师David Borsook博士)，熟练应用动态因果关系 神经成像数据分析建模(导师利诺·贝塞拉博士和合作者卡尔·弗里斯顿博士)， 并成为FUS介导的血脑屏障开放方面的专家(导师内森·麦克丹诺德博士)。 该提案中的研究目的是基于托德博士在磁共振神经成像和FUS方面的经验 在培训领域为他提供直接经验的同时，也为他提供了应用程序方面的经验。研究工作将 开发和验证一种使用FUS的非侵入性神经调节的新方法的方法学- 介导血脑屏障开放，将神经递质传递到目标大脑区域。目标人群 神经递质传递法将被用来研究啮齿动物疼痛网络的调制。 兴奋性(谷氨酸)和抑制性(GABA)神经递质将被传递到疼痛的结节 健康和神经病理性疼痛大鼠的神经网络(丘脑和躯体感觉皮质)。其影响将是 使用三种功能互补方法在整个疼痛网络中进行测量 磁共振成像(FMRI)、动态因果模型(DCM)和行为测试。 这项工作将推动托德博士在成为独立科学家的道路上前进。培训 组件将为托德博士提供必要的系统水平神经科学知识 使用MRI和FUS进行脑相关研究的职业；研究部分将开发一个新的 非侵入性神经调节的方法，这将成为未来工作和拨款申请的基础。